title: Novel markers of squamous differentiation in the urinary bladder.
abstract: Urinary bladder squamous cell carcinoma and urothelial carcinoma with squamous differentiation are often high-grade and high-stage tumors that are thought to be associated with a poorer prognosis and response to therapy compared with urothelial carcinoma without divergent differentiation. Therefore, recognition of a squamous component is increasingly important in guiding prognosis and therapy. We investigated the expression of MAC387, desmoglein-3, and TRIM29 in pure squamous cell carcinoma and urothelial carcinoma with squamous differentiation to determine whether they have utility as diagnostic biomarkers for squamous differentiation. Eighty-four cases were retrieved from participating institutions including 51 pure urinary bladder squamous cell carcinomas and 33 urothelial carcinomas with squamous differentiation. MAC387, desmoglein-3, and TRIM29 antibodies demonstrated positive staining in pure squamous cell carcinoma in 51 (100%), 46 (90%), and 48 (93%) cases, respectively. Urothelial carcinoma with squamous differentiation showed reactivity for MAC387, desmoglein-3, and TRIM29 in the squamous component for 32 (97%), 26 (79%), and 32 (97%) cases, respectively. MAC387 demonstrated a sensitivity of 99% and a specificity of 70% for squamous differentiation, whereas desmoglein-3 yielded a sensitivity of 86% and a specificity of 91%. No urothelial component showed greater than 10% labeling for desmoglein-3. TRIM29 labeling showed a sensitivity of 95%, but a poorer specificity of 33%. In summary, MAC387 and desmoglein-3 are reliable diagnostic markers for supporting the morphologic impression of squamous differentiation in urinary bladder carcinoma. Desmoglein-3 shows high specificity, whereas TRIM29 was most likely to demonstrate labeling in areas without light microscopically recognizable squamous differentiation.
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Pathology, Nanjing Medical University Affiliated Nanjing Hospital (Nanjing First Hospital), Nanjing 210006, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Huang
authors.forename: Sean R
authors.initials: SR
authors.lastname: Williamson
authors.forename: Qiu
authors.initials: Q
authors.lastname: Rao
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Beltran
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.forename: John N
authors.initials: JN
authors.lastname: Eble
authors.forename: David J
authors.initials: DJ
authors.lastname: Grignon
authors.forename: Muhammad T
authors.initials: MT
authors.lastname: Idrees
authors.forename: Robert E
authors.initials: RE
authors.lastname: Emerson
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Zhou
authors.forename: Shaobo
authors.initials: S
authors.lastname: Zhang
authors.forename: Lee Ann
authors.initials: LA
authors.lastname: Baldridge
authors.forename: Noah M
authors.initials: NM
authors.lastname: Hahn
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Wang
authors.forename: Michael O
authors.initials: MO
authors.lastname: Koch
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D040502:Calgranulin B / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000378:metabolism; D051184:Desmoglein 3 / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D011379:Prognosis; D012680:Sensitivity and Specificity; D014157:Transcription Factors / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D040502:Calgranulin B; D004268:DNA-Binding Proteins; D051184:Desmoglein 3; C087296:TRIM29 protein, human; D014157:Transcription Factors
keywords: Desmoglein-3; MAC387; Squamous cell carcinoma; TRIM29; Urinary bladder; Urothelial carcinoma with mixed differentiation